Assessment of Cardiac Adverse Events following COVID-19 Vaccination by Speckle Tracking Echocardiography (preprint)

Background: Cardiac discomfort has been reported periodically in COVID-19 vaccinated individuals. Thus, this study aimed to evaluate the role of myocardial strains in the early assessment of the clinical presentations after COVID-19 vaccination. Methods and Results: Totally, 121 subjects who received at least one dose of vaccine within 6 weeks underwent laboratory tests and echocardiogram. Two-dimensional speckle tracking echocardiography (2D-STE) was implemented to analyze changes in the left ventricular myocardium. After vaccination, 66 individuals (55.4 ± 17.4 years) developed cardiac discomfort, such as chest tightness, palpitations, dyspnea, and chest pain. All had normal serum levels of creatine phosphokinase, creatine kinase myocardial band, troponin, N-terminal pro b-type natriuretic peptide, platelets, and D-dimer. Left ventricular ejection fraction in the symptomatic group (71.41% ± 7.12%) and the control group (72.18% ± 5.11%) (p = 0.492) were normal. Use of 2D-STE presented global longitudinal strain (GLS) and global circumferential strain (GCS) were reduced in symptomatic group (17.86% ± 3.22% and 18.37% ± 5.22%) compared to control group (19.54% ± 2.18% and 20.73% ± 4.09%) (p = 0.001 and p = 0.028). Conclusion: COVID-19 vaccine-related cardiac adverse effects can be assessed early by 2D-STE. The prognostic implications of GLS and GCS enable evaluation of subtle changes in myocardial function after vaccination.

From Academic Resilience to Academic Burnout among International University Students during the Post-COVID-19 New Normal: An Empirical Study in Taiwan.

(1) Background: In the context of the COVID-19 pandemic, it is imperative for higher education institutions to understand the socio-psychological issues of international students, a potentially vulnerable population on campuses, to assist them in pursuing their academic path while maintaining their psychological well-being. The objectives of this study were to determine the prevalence of academic burnout among international university students in Taiwan during the new normal and to explore the protective role of academic resilience. (2) Methods: Three hundred and eighty-three international university students in Taiwan were recruited and surveyed via the online self-administered questionnaire during the Fall semester of the 2022-2023 academic year. The data of sociodemographic characteristics, academic burnout, and academic resilience were collected and analyzed. (3) Results: The overall prevalence of high academic burnout was 12.01%. The majority of participants perceived significant depression and anxiety (detrimental factors) but moderate to high perception of academics and relationships (protective factors). There were significant relationships between resilience components and burnout symptoms. (4) Conclusions: Resilience may help to reduce burnout among international university students during the post-COVID-19 new normal, thereby protecting their mental health.

Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant (preprint)

Emergence of SARS-CoV-2 variants, including the globally successful B.1.1.7 lineage, suggests viral adaptations to host selective pressures resulting in more efficient transmission. Although much effort has focused on Spike adaptation for viral entry and adaptive immune escape, B.1.1.7 mutations outside Spike likely contribute to enhance transmission. Here we used unbiased abundance proteomics, phosphoproteomics, mRNA sequencing and viral replication assays to show that B.1.1.7 isolates more effectively suppress host innate immune responses in airway epithelial cells. We found that B.1.1.7 isolates have dramatically increased subgenomic RNA and protein levels of Orf9b and Orf6, both known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein required for RNA sensing adaptor MAVS activation, and Orf9b binding and activity was regulated via phosphorylation. We conclude that B.1.1.7 has evolved beyond the Spike coding region to more effectively antagonise host innate immune responses through upregulation of specific subgenomic RNA synthesis and increased protein expression of key innate immune antagonists. We propose that more effective innate immune antagonism increases the likelihood of successful B.1.1.7 transmission, and may increase in vivo replication and duration of infection.

CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes. (preprint)

The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis of those functions, remain unknown. Here, we report an atomic model for full-length Nsp2 obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. The resulting structure reveals a highly-conserved zinc ion-binding site, suggesting a role for Nsp2 in RNA binding. Mapping emerging mutations from variants of SARS-CoV-2 on the resulting structure shows potential host-Nsp2 interaction regions. Using structural analysis together with affinity tagged purification mass spectrometry experiments, we identify Nsp2 mutants that are unable to interact with the actin-nucleation-promoting WASH protein complex or with GIGYF2, an inhibitor of translation initiation and modulator of ribosome-associated quality control. Our work suggests a potential role of Nsp2 in linking viral transcription within the viral replication-transcription complexes (RTC) to the translation initiation of the viral message. Collectively, the structure reported here, combined with mutant interaction mapping, provides a foundation for functional studies of this evolutionary conserved coronavirus protein and may assist future drug design.

CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes (preprint)

The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis of those functions, remain unknown. Here, we report an atomic model for full-length Nsp2 obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. The resulting structure reveals a highly-conserved zinc ion-binding site, suggesting a role for Nsp2 in RNA binding. Mapping emerging mutations from variants of SARS-CoV-2 on the resulting structure shows potential host-Nsp2 interaction regions. Using structural analysis together with affinity tagged purification mass spectrometry experiments, we identify Nsp2 mutants that are unable to interact with the actin-nucleation-promoting WASH protein complex or with GIGYF2, an inhibitor of translation initiation and modulator of ribosome-associated quality control. Our work suggests a potential role of Nsp2 in linking viral transcription within the viral replication-transcription complexes (RTC) to the translation initiation of the viral message. Collectively, the structure reported here, combined with mutant interaction mapping, provides a foundation for functional studies of this evolutionary conserved coronavirus protein and may assist future drug design.

Reducing travel-related SARS-CoV-2 transmission with layered mitigation measures: Symptom monitoring, quarantine, and testing (preprint)

Balancing the control of SARS-CoV-2 transmission with the resumption of travel is a global priority. Current recommendations include mitigation measures before, during, and after travel. Pre- and post-travel strategies including symptom monitoring, testing, and quarantine can be combined in multiple ways considering different trade-offs in feasibility, adherence, effectiveness, cost and adverse consequences. Here we use a mathematical model to analyze the expected effectiveness of symptom monitoring, testing, and quarantine under different estimates of the infectious period, test-positivity relative to time of infection, and test sensitivity to reduce the risk of transmission from infected travelers during and after travel. If infection occurs 0-7 days prior to travel, immediate isolation following symptom onset prior to or during travel reduces risk of transmission while traveling by 26-30%. Pre-departure testing can further reduce risk if testing is close to the time of departure. For example, testing on the day of departure can reduce risk while traveling by 37-61%. For transmission risk after travel with infection time up to 7 days prior to arrival at the destination, isolation based on symptom monitoring reduced introduction risk at the destination by 42-56%. A 14-day quarantine after arrival, without symptom monitoring or testing, can reduce risk by 97-100% on its own. However, a shorter quarantine of 7 days combined with symptom monitoring and a test on day 3-4 after arrival is also effective (95-99%) at reducing introduction risk and is less burdensome, which may improve adherence. To reduce the risk of introduction without quarantine, optimal test timing after arrival is close to the time of arrival; with effective quarantine after arrival, testing a few days later optimizes sensitivity to detect those infected immediately before or while traveling. These measures can complement recommendations such as social distancing, using masks, and hand hygiene, to further reduce risk during and after travel.